This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy (NCT01480297), a na phase 2 study. The primary outcome is Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01480297 |
| Phase | Phase 2 |
| Condition | Peripheral Neuropathy, Type 1 Diabetes |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan |
| Results posted | Yes |
2. Clinical Question
Population
People with type 1 diabetes and signs and symptoms of peripheral neuropathy, described for the primary outcome as type 1 diabetes with painful neuropathy.
Intervention
All subjects took salsalate for 12 weeks. The stated regimen was 3 grams daily, divided into 3 doses of 1 gram with breakfast, lunch and dinner.
Comparator
There was no comparator group: the record describes a single-group study in which all subjects received salsalate. Allocation is listed as NA, and masking as none.
Primary question
The study set out to examine the effect of treatment on intra-epidermal nerve fiber density, measured at the thigh and ankle at baseline and after 12 weeks. Numerical outcome results are not reported in the registry record.
This is a question about measurements over time in a small, single-group pilot, rather than a randomized comparison between salsalate and a control treatment. The stated study aim also mentions markers of neuropathic pain, but the record lists one outcome measure, intra-epidermal nerve fiber density, and gives no numerical result for it. It therefore does not allow a reader to assess the amount or direction of any observed change from the posted results.
The record identifies a treatment regimen and measurement schedule, but does not report a separate comparison group, a blinding procedure, or an analysis of the outcome. The clinical question can be described from the stated aim and endpoint; an answer about the observed outcome cannot be reconstructed from those details alone. Any interpretation should keep that distinction clear: a planned measurement is not itself evidence of a particular result, and a within-group observation would not be the same as an estimate from a controlled comparison.
3. Trial Design
This completed phase 2 study is recorded as a single-group trial with allocation listed as NA and no masking. Enrollment was 8. The sponsor was the University of Michigan. The study began in 2011-11 and primary completion was recorded in 2012-04. These registry entries describe the study structure and status, but do not supply an analysis of the primary outcome.
All subjects received salsalate. The arm description specifies 3 grams daily, taken as 3 divided doses of 1 gram with breakfast, lunch and dinner. There is no separate placebo, usual-care or untreated group described in the record. As a result, the design does not create a like-for-like treatment comparison. Changes measured from baseline to follow-up, if available, would describe measurements during treatment in this group; they would not by themselves isolate a treatment effect from other influences over time.
The primary outcome was intra-epidermal nerve fiber density, expressed as fibers per mm. It was measured at the thigh and ankle at baseline and after 12 weeks. The outcome description says that means and standard deviations are shown, but the numerical means and standard deviations are not reported in the registry record. The record lists one outcome measure and no analyses.
The available details support calling this a small pilot with repeated measurements and no comparator, but they do not establish why this design or enrollment target was chosen. Sample-size justification, eligibility criteria beyond the stated population, adherence, and a fuller protocol description are not reported in the registry record. The study is marked completed; that status does not substitute for posted outcome estimates or an explanation of how they were analyzed.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Salsalate |
|---|---|
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Type 1 diabetes with painful neuropathy
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: adults with type 1 diabetes and painful peripheral neuropathy
| Characteristic | Unit | Salsalate |
|---|---|---|
| Participants analysed | 8 | |
| Age, Continuous | Years | 57.0 (SD 5.7) |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 7 |
| Age, Categorical: >=65 years | Participants | 1 |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 5 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 8 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm, measured over Baseline and 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | fibers per mm |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is intra-epidermal nerve fiber density, abbreviated IENFD in the outcome description and expressed in fibers per mm. The study measured it at the thigh and ankle at baseline and after 12 weeks of salsalate treatment. The record describes this endpoint as a measure of peripheral neuropathy in people with type 1 diabetes and painful neuropathy, and states that means and standard deviations are shown.
Because the endpoint is continuous, its value can be summarized by a mean, while a standard deviation describes the spread of individual measurements around that mean. In general, reporting both helps readers distinguish the average measurement from the variability among participants. Neither summary, on its own, describes the uncertainty in an estimated treatment effect or the statistical evidence for a change.
Measuring at baseline and follow-up makes it possible in principle to describe how the recorded measurements differ over time. Measuring at the thigh and ankle also means the anatomical location matters when interpreting an outcome: values from different sites should not be treated as interchangeable without an analysis plan. The registry record does not report numerical site-specific measurements, a change estimate, a confidence interval, or a test of change. The rationale for choosing this endpoint beyond its stated role as a neuropathy measure is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted description identifies the primary outcome and the planned measurement times, but numerical outcome results are not reported in the registry record. In particular, the record does not give the baseline or 12-week means and standard deviations for the thigh or ankle, nor a change estimate, confidence interval, or p-value. Without those results, the direction and size of any observed difference cannot be evaluated from the registry record.
That distinction matters because a description of what investigators measured is not a report of what they found. The endpoint title, measurement schedule and stated study aim establish the subject of the analysis, but they cannot tell readers whether values increased, decreased or remained similar. No result should be inferred from the fact that the trial is marked completed or from its enrollment count.
The design also constrains what a result could mean. This was a single-group study with no comparator described. In general, a change between baseline and follow-up in one group can be described as a temporal change among the measured participants. It cannot, by itself, distinguish a treatment-related change from other changes occurring during the same period. That concern is different from statistical precision: even a precisely estimated within-group change would not create the missing concurrent comparison.
Enrollment was 8, making the study a small pilot in the ordinary descriptive sense. In general, measurements from a small group can be sensitive to individual observations, and estimates may be imprecise. However, the exact precision cannot be judged because the outcome values and uncertainty estimates are not reported in the registry record. It would also be inappropriate to infer a study's statistical power from enrollment alone.
The posted outcome description says that means and standard deviations are shown, but the numerical values are not available in the record details. The record lists no analyses. It does not report how the two anatomical sites or repeated measurements were handled statistically, whether any adjustment was made, or how missing observations were treated. Those gaps prevent readers from checking the relationship between the descriptive results and any inferential conclusion.
Accordingly, the defensible interpretation is limited: the study planned to assess IENFD at two sites before and after 12 weeks of salsalate in a single group, but its numerical primary outcome result and statistical analysis are not reported in the registry record. The record cannot establish either the magnitude of a change or its uncertainty, and it cannot support a controlled comparison.
9. Statistical Methods Explained
The registry record gives a limited statistical description. It identifies a continuous primary outcome, specifies means and standard deviations as the summaries, and states that measurements were taken at baseline and after 12 weeks at the thigh and ankle. It lists one outcome measure and no analyses. A detailed statistical analysis plan is not reported in the registry record, so the methods below distinguish what the record states from general statistical considerations.
What does a mean summarize?
A mean summarizes the central level of a set of measurements. For IENFD, the mean would represent the average fibers-per-mm measurement for the participants contributing data at a particular site and time. It is a descriptive summary, not automatically a treatment-effect estimate. To estimate change, an analysis needs to define how baseline and follow-up measurements are compared and which participants and observations are included.
A standard deviation describes how dispersed measurements are around their mean. It is not the same as a confidence interval: the standard deviation characterizes variation among observations, whereas a confidence interval expresses uncertainty around an estimated quantity. In general, the interval's width depends on the data and the analysis. No confidence interval is reported in the registry record, and none can be recovered from the study description alone.
How do repeated measurements affect interpretation?
Measurements at baseline and follow-up on the same participants are related rather than independent. In general, an analysis of change can account for this pairing by using each participant's measurements together. The within-participant relationship can affect the uncertainty of an estimated average change. The registry record does not say whether a paired analysis, a model for repeated measurements, or another method was used. It also does not report a numerical change estimate.
The outcome was recorded at the thigh and ankle. These are distinct anatomical locations, so a statistical report would ideally make clear whether results are presented separately by site, combined according to a specified method, or evaluated using a model that includes site. The record describes measurement at both locations but does not report how they were handled analytically. Readers should not assume that the two sites were pooled or that one was selected as the principal analysis.
What can a single-group design estimate?
In a single-group study, baseline and follow-up measurements can describe how outcomes changed among participants over the observation period. In general, a controlled trial adds a concurrent group to help distinguish changes associated with the study treatment from changes that might have occurred over time for other reasons. This record describes no comparator group, so it does not support a randomized between-group estimate. A within-group change, even if it were reported, would answer a different question from a treatment-versus-control contrast.
Allocation is recorded as NA and masking as none. Those features are consistent with the stated single-group structure, but the record does not give further details about concealment, assessor procedures, or implementation. Such details should not be inferred. The absence of a comparator also means there is no control-group estimate to interpret alongside the treated group's measurements.
What does the sample-size illustration represent?
The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that non-time-to-event illustrations are stated as participants per arm. This is a planning exercise, not observed power. It does not describe the original design rationale, and its hypothetical two-arm structure is not the same as this single-group trial. Numerical sample-size illustration results and the observed effect used for them are not reported in the registry record. The study's own sample-size justification is not reported in the registry record.
In general, a planning calculation asks how much information a future design might need under specified assumptions. Such calculations depend on the target effect, variability, allocation, significance level and power target. If those assumptions differ from the eventual study or the effect is estimated imprecisely, the resulting planning figure may not translate directly to another setting. The illustration should not be read as evidence that the completed study had adequate power, and it cannot replace an estimate and confidence interval for the outcome actually observed.
What information is missing for inference?
The registry record lists no analyses and does not report numerical endpoint results. It therefore does not provide the information needed to assess an inferential test, model fit, or the precision of a change estimate. The statistical analysis plan, handling of repeated measurements, and treatment of missing data are not reported in the registry record. Nor does the record state whether the analysis was adjusted for any covariates. These omissions do not establish that a particular method was or was not used outside the registry; they mean only that the method cannot be evaluated from the registry record.
In general, statistical inference depends on both the observed data and the assumptions of the chosen method. For a small pilot, it is especially useful to show the underlying descriptive summaries and an uncertainty interval rather than relying only on a significance test. Here those summaries and inferential results are not reported in the registry record. The sound reading is therefore descriptive about the design and endpoint, and explicitly uncertain about outcome findings.
10. Multiplicity, Missing Data and Analysis Populations
The record lists one outcome measure, IENFD, and describes measurements at the thigh and ankle at baseline and after 12 weeks. It does not explain whether the locations were treated as separate endpoints, whether one location was designated as primary for inference, or whether a combined analysis was planned. The registry record does not report a multiplicity procedure or a statistical analysis plan. It is therefore not possible to determine whether the number of outcome comparisons affected the interpretation of any inferential results.
In general, multiplicity arises when several outcomes, time points, sites, or statistical tests are examined. The more opportunities there are to identify a result, the more important it is to specify in advance which comparisons are confirmatory and how any additional testing will be interpreted. That general issue should not be mistaken for evidence that this study performed multiple tests; the record does not list analyses.
Missing-data methods and the analysis population are also not reported in the registry record. The enrollment count is 8, but the record does not say how many participants contributed measurements at each site and time, whether anyone discontinued, or how unavailable measurements were handled. It does not specify whether analysis was based on all enrolled participants or another population. These details matter because the number and pattern of observed measurements can affect a mean, a change estimate and its uncertainty.
In general, missing observations can affect interpretation when the participants with recorded follow-up measurements differ from those without them. A complete description would state the amount of missingness and the method used, rather than leave readers to infer how the analysis was conducted. No such information is reported in the registry record, so the impact of missing data cannot be assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Salsalate | 1 | 8 | 12.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Salsalate | 6 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Salsalate |
|---|---|---|
| Severe Hypoglycemia | Metabolism and nutrition disorders | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Salsalate |
|---|---|---|
| Tinnitus | Ear and labyrinth disorders | 3 of 8 |
| Upper Respiratory Symptoms | Respiratory, thoracic and mediastinal disorders | 2 of 8 |
| Increased Bleeding from Biopsy Site | Surgical and medical procedures | 1 of 8 |
| Hot Flashes | Endocrine disorders | 1 of 8 |
| Cataract Removal | Eye disorders | 1 of 8 |
| Skin Biopsy of Suspicious Lesion | Skin and subcutaneous tissue disorders | 1 of 8 |
Serious events with the highest arm-level rate: severe hypoglycemia (12.5%).
The safety summary lists 8 participants at risk for serious adverse events, with 1 affected. It lists 8 at risk for other adverse events, with 6 affected. The serious adverse-event terms include severe hypoglycemia at 12.5%. These are counts and a percentage reported in the registry record; they do not provide a comparative estimate because the study has no comparator group.
The serious-event count and the other-adverse-event count refer to different categories in the summary and should not be added together or treated as interchangeable. The record does not give a full event-by-event account, timing, duration, outcome, or attribution to treatment. The number of deaths is not reported in the registry record. The listed severe hypoglycemia term is a safety description, not a measure of the primary IENFD outcome.
In general, safety counts in a small single-group study describe events recorded among participants who received the intervention. Without a control group, they cannot establish whether an event occurred more often because of treatment than it would have otherwise. The counts also do not by themselves characterize an individual participant's risk. The record's limited safety summary should therefore be read as a description of reported events, not as a comparative safety analysis.
12. What the Result Does, and Does Not, Mean
This study's registry description establishes that investigators enrolled 8 participants in a completed phase 2, single-group study of salsalate for people with type 1 diabetes and painful peripheral neuropathy. The stated regimen was 3 grams daily for 12 weeks. The primary outcome was IENFD, measured at the thigh and ankle at baseline and after treatment. Those details define the population, intervention, design and planned endpoint.
They do not establish what happened to the endpoint. The numerical means and standard deviations, any estimate of change, and any inferential results are not reported in the registry record. The registry record therefore does not show the direction, magnitude or precision of an observed IENFD change. It would be inaccurate to describe the intervention as having improved, worsened or left the endpoint unchanged on the basis of this record.
Even if a within-group change were available, the single-group design would limit what it could establish. In general, repeated measurements can document change over time among participants, but without a comparator that change cannot be separated from other influences over the same period. This design is consequently different from a randomized comparison and should not be described as one.
The sample-size illustration described in the record is a planning exercise, not observed power. It assumes a hypothetical two-arm allocation, whereas the trial itself is recorded as single group. It should not be used to claim that this completed study was adequately powered, and its assumptions do not supply the missing outcome estimate.
The safety summary reports serious and other adverse-event counts, including severe hypoglycemia as a listed serious term. These figures describe events in the enrolled group and do not provide a controlled comparison or causal attribution. Overall, the record supports a clear account of the study's design and measurement plan, but not a conclusion about the primary outcome or a comparative treatment effect. Those conclusions require outcome results and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial matters statistically because its design makes the distinction between measurement and comparison especially visible. It measured a continuous outcome at baseline and follow-up in a single group, with observations at the thigh and ankle. Such a structure can produce useful descriptive information, but a change over time is not equivalent to a treatment-versus-control effect. Recognizing that distinction is essential when reading small pilot studies.
The trial also illustrates why endpoint summaries and analysis details matter. A mean and standard deviation can describe the distribution of measurements, but readers also need to know how repeated observations were compared, how different sites were handled, and what uncertainty surrounds an estimate. The registry record names the descriptive summaries but does not report their values or any analysis. Consequently, the principal statistical result cannot be evaluated.
Enrollment of 8 makes precision a particularly relevant question, although precision cannot be quantified without the outcome data. In general, smaller studies may yield uncertain estimates, and the observed values of individual participants can have an appreciable influence. A confidence interval, together with transparent descriptive results, would help readers judge uncertainty if those results were available. A significance test alone would not address design limitations or establish a controlled effect.
The sample-size illustration described by the registry record offers another useful distinction: a planning calculation is not observed power, and its hypothetical two-arm assumptions do not match the recorded single-group design. The illustration cannot fill the gap left by absent outcome results or justify an inference about efficacy.
For biostatisticians and clinical researchers, this record is a reminder to separate four questions: what was planned, what was measured, what was observed, and what comparison the design can support. Here, the first two are described, while numerical observations and analyses are not reported. The result is a transparent but incomplete statistical account.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most immediate limitation for interpreting this trial from the registry record is the absence of numerical primary outcome results. Although the outcome description states that means and standard deviations are shown, the values are not reported in the registry record. There is no reported estimate of change, uncertainty interval, or test result. The primary outcome therefore cannot be quantitatively interpreted.
The single-group design is a further limitation for causal interpretation. All subjects received salsalate, and no comparator is described. A before-and-after change, if reported, could describe the observed course in the group, but it would not provide a controlled estimate of treatment effect. The record also lists no masking.
Enrollment was 8, so the study is small. The amount of statistical uncertainty cannot be determined without the actual measurements and analysis, and no inference about power can be made from enrollment alone. The registry record does not report a sample-size justification. A separate planning illustration is described, but its hypothetical equal allocation between two arms does not match the recorded single-group design and should not be treated as observed power.
Other information needed to assess the endpoint analysis is not reported in the registry record. This includes how the thigh and ankle measurements were handled, how baseline and follow-up observations were compared, the analysis population, and the approach to missing data. The record does not list analyses. It also does not give enough safety detail to assess event timing, duration, outcomes or attribution. These limitations concern what can be learned from the registry record and should not be taken as evidence about procedures or results that may exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy — NCT01480297.
- Registry record last updated 2015-04-24; status last verified 2015-04.
- Results first posted 2015-04-24.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01480297 is a completed phase 2, single-group pilot study sponsored by the University of Michigan. The record describes enrollment of 8 people with type 1 diabetes and painful peripheral neuropathy. All subjects received salsalate at 3 grams daily, divided into 3 doses of 1 gram, for 12 weeks. Allocation is listed as NA and masking as none.
The primary outcome was IENFD, expressed in fibers per mm and measured at the thigh and ankle at baseline and after 12 weeks. The record says means and standard deviations are shown, but numerical outcome results and analyses are not reported in the registry record. No comparator group is described, so the design does not support a controlled treatment comparison.
The safety summary records 1 serious adverse-event-affected participant among 8 at risk and 6 participants with other adverse events among 8 at risk. Severe hypoglycemia is listed among serious terms at 12.5%. Further details on analysis methods, missing data, and event attribution are not reported in the registry record.